AB0640 PREVALENCE AND DETERMINANT FACTORS OF ENDOTHELIAL DYSFUNCTION IN ANCA ASSOCIATED VASCULITIS

Abstract

Background: Atherosclerosis and its complications are one the leading cause of death in patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vas-culitis (AAVs), despite the recent remarkable improvements in prognosis. The mechanism by which atherosclerosis is accelerated in these diseases is not explained by the classical cardiovascular risk factors (CVRFs) and is still under investigation. Objectives: To evaluate the prevalence of endothelial dysfunction (ED) in AAV patients and to identify the determinant factors of endothelial responses among vasculitis characteristics, such as ANCA status and organ involvement. Methods: Thirty patients (15 men and 15 women) with AAVs [13 with eosin-ophilic granulomatosis with polyangiitis (EGPA), 7 with granulomatosis with polyangiitis (GPA), 10 with microscopic polyangiitis (MPA)] were enrolled in the study. For all subjects CVRFs, blood pressure, lipid profile, renal function, acute phase reactants, ANCA status and titers were recorded at diagnosis and at the enrollement in the study. Vasculitis disease activity was measured using the Birmingham Vasculitis Activity Score (BVAS) and organ damage was assessed with the vasculitis damage index (VDI). The prognosis was evaluated through the Five Factor Score (FFS). Patients were excluded from the study if they had previous cardiovascular or cerebrovascular events, liver failure, end stage renal disease under hemodyalisis, or cancer. Microvascular peripheral dysfunction was assessed by pulse amplitude tonometry (PAT) of the small digital artery. In particular, Log-transformed reactive hyperemia index (LnRHI) was evaluated using the EndoPAT2000 device: values of Ln-RHI < 0.51 were considered indicative of peripheral ED. Results: At diagnosis, 23 subjects (76.7%) were ANCA positive (8 c-ANCA+, 15 pANCA+), and at the enrollment in the study 10 patients (33.3%) were still seropositive. Nineteen patients (63.3%) had inactive disease (BVAS=0), 7 (23.3%) were in low disease activity (1≤BVAS≤2) and 4 (13.3%) had an active disease (BVAS≥3). The presence of ED was documented in 9 AAV patients (30%). AAV patients with ED had higher C-reactive protein (CRP) values at diagnosis compared to subjects without ED (p=0.05). Moreover, patients with altered endothe-lial response were in higher percentage smokers (55.6%) and ANCA positive at enrollment (44.4%), compared to subjects with normal Ln-RHI (28.6%-p=0.12; 19%, p=0.15 respectively). There were no differences regarding age and other traditional CVRFs, disease duration, BMI, BVAS, VDI, FFS. There was an inverse correlation between CRP values at diagnosis and LnRHI (r=-0.42, p=0.04). In multiple logistic regression analysis, ANCA positivity at enrollment [OR (95% CI) = 15.68 (0.98-250.28)] (p=0.05), and higher CRP concentrations [OR (95% CI) = 1.03 (1.00-1.06)] (p=0.03) were independently associated with the presence of peripheral ED. Conclusion: As observed in other chronic infammatory autoimmune diseases, ED occurs in AAVs and is mainly related to the chronic systemic infammation and seems to be also influenced by ANCA positivity, which is probably involved in the accelerated endothelial cell damage. Further studies are needed to clarify the role of vasculitis related characteristics in the atherosclerotic process.